Our analysis of events in immediate hypersensitivity focuses on human and animal models of allergic responses, mechanisms of mediator action, and pharmacologic approaches to allergic diseases. The areas under investigation include asthma, allergic rhinitis, anaphylaxis, urticaria, and mastocytosis. Employing monoclonal antibodies directed at cyclic GMP, the pattern of cells in guinea pig lung responding to histamine stimulation has been identified. Histamine causes all cells to increase their cytoplasmic cyclic GMP with an increased concentration near the nuclear membrane. In mouse lung, a population of dendritic cells has been identified which is found in the mucous membrane and is a potent antigen presenting cell. Ketotifen has been found to prevent histamine release from mast cells in patients with physical urticarias. Histamine levels in plasma are diagnostic of systemic mastocytosis if consistently elevated. The mechanism for progesterone-related anaphylaxis has been examined and remains unclear while a second progesterone-sensitive subject with anaphylaxis responded to LHRH analogue therapy. Microvascular permeability in skin is increased by histamine, serotonin, and bradykinin but does not appear to contribute to the edema seen in late phase responses. Plasma histamine from patients in gram negative sepsis and shock is reduced below normal.